Browsing by Author "Tapia Castillo, Alejandra"

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    Aldosterona e IL-17 en la génesis de la hipertensión arterial mineralocorticoídea, un estudio ex vivo
    (2016) Vecchiola Cárdenas, Andrea Paola; Cristóbal Fuentes, Z.; Muñoz Durango, Natalia; Tapia Castillo, Alejandra; González Gómez, Luis M.; Baudrand Biggs, René; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Kalergis Parra, Alexis Mikes; Carlos, F.; Lagos, A.; Fardella B., Carlos; Vecchiola Cárdenas, Andrea Paola; Cristóbal Fuentes, Z.; Muñoz Durango, Natalia; Tapia Castillo, Alejandra; González Gómez, Luis M.; Baudrand Biggs, René; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Kalergis Parra, Alexis Mikes; Carlos, F.; Lagos, A.; Fardella B., Carlos
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    Citosine-Adenine-Repeat Microsatellite of 11 beta-hydroxysteroid dehydrogenase 2 Gene in Hypertensive Children
    (OXFORD UNIV PRESS, 2016) Valdivia, Carolina; Carvajal, Cristian A.; Campino, Carmen; Allende, Fidel; Martinez Aguayo, Alejandro; Baudrand, Rene; Vecchiola, Andrea; Lagos, Carlos F.; Tapia Castillo, Alejandra; Fuentes, Cristobal A.; Aglony, Marlene; Solari, Sandra; Kalergis, Alexis M.; Garcia, Hernan; Owen, Gareth I.; Fardella, Carlos E.
    BACKGROUND
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    Clinical, Biochemical, and Genetic Characteristics of "Nonclassic" Apparent Mineralocorticoid Excess Syndrome
    (2019) Tapia Castillo, Alejandra; Baudrand Biggs, René; Vaidya, Anand; Campino Johnson, María del Carmen; Allende, Fidel; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Fardella B., Carlos; Solari, Sandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Valdivia, Carolina; Tapia Castillo, Alejandra; Baudrand Biggs, René; Vaidya, Anand; Campino Johnson, María del Carmen; Allende, Fidel; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Fardella B., Carlos; Solari, Sandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Valdivia, Carolina
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    Hypertensive Patients That Respond to Aldosterone Antagonists May Have a Nonclassical 11β-HSD2 Deficiency.
    (2017) Tapia Castillo, Alejandra; Carvajal Maldonado, Cristián Andrés; Allende, Fidel; Campino Johnson, María del Carmen; Fardella B., Carlos
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    Polymorphisms in the RAC1 Gene Are Associated With Hypertension Risk Factors in a Chilean Pediatric Population
    (OXFORD UNIV PRESS, 2014) Tapia Castillo, Alejandra; Carvajal, Cristian A.; Campino, Carmen; Vecchiola, Andrea; Allende, Fidel; Solari, Sandra; Garcia, Lorena; Lavanderos, Sergio; Valdivia, Carolina; Fuentes, Cristobal; Lagos, Carlos F.; Martinez Aguayo, Alejandro; Baudrand, Rene; Aglony, Marlene; Garcia, Hernan; Fardella, Carlos E.
    The GTPase Rac1 has been implicated in hypertension as a modulator of mineralocorticoid receptor activity. Our aim is to investigate the frequency of polymorphisms rs10951982 (intron 1, G > A) and rs836478 (intron 3, T > C) in the RAC1 gene and perform association studies with clinical and biochemical parameters in a Chilean pediatric cohort.
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    Primary aldosteronism in a hispanic cohort: responses to mineralocorticoid receptor antagonism and remission in a case
    (2025) Tapia Castillo, Alejandra; Vecchiola Cárdenas, Andrea Paola; Quiñones, Paola; Baudrand Biggs, Rene Felipe; Uslar Nawrath, Thomas Hermann; Delgado García, José Frobel; Carvajal Maldonado, Cristian Andrés; Fardella Bello, Carlos Enrique
    Background: Primary aldosteronism (PA) is the main cause of secondary arterial hypertension. In this study, we present the medical treatment of Hispanic patients with PA followed for up to 5 years, highlighting the complete cure with pharmacological treatment in one of our patients. Methods: We studied 32 PA patients, followed every 6 months after starting MRA. A clinical response was the normalization of blood pressure (BP) in the absence of other antihypertensive drugs. The biochemical response was considered with normalization of potassium and renin. Responses to treatment were compared using the defined daily dose (DDD). The effect of MRA was evaluated in vitro. The HAC15 cells were cultured and stimulated with aldosterone and spironolactone for 24-72h, and the apoptotic cell death was measured. Results: At 12 months posttreatment with MRA, 68% of the patients had a total clinical response, and 67% had a total biochemical response. Response to MRA treatment reduced DDD by an average of 74%. Additionally, we observed one PA patients treated with spironolactone after three years, he presented a pharmacological cure with normalization of aldosterone and renin without treatment with spironolactone. The in vitro study shows that spironolactone increased early apoptosis in a 60% and late apoptosis in a 50%. Conclusion: These results suggest the importance of timely diagnosis of PA and specific treatment with MRA, especially in patients with a poor response to treatment. Moreover, remission of PA may occur in some patients after spironolactone treatment due to its suggestive role as an apoptotic agent.
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    Progressive 11β-hydroxysteroid dehydrogenase type 2 insufficiency as kidney function declines
    (2024) Uslar N., Thomas; Newman, Andrew J.; Tapia Castillo, Alejandra; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; Allende, Fidel; Solari, Sandra; Tsai, Laura C.; Milks, Julia; Cherney, Michael; Stouffer, David G.; Auchus, Richard; Brown, Jenifer M.; Baudrand Biggs, René; Vaidya, Anand
    Background It has been postulated that chronic kidney disease (CKD) is a state of relative 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta HSD2) insufficiency, resulting in increased cortisol-mediated mineralocorticoid receptor (MR) activation. We hypothesized that relative 11 beta HSD2 insufficiency manifests across a wide spectrum of progressively declining kidney function, including within the normal range. Methods Adult participants were recruited at 2 academic centers. A discovery cohort (n = 500) enrolled individuals with estimated glomerular filtration rate (eGFR) ranging from normal to CKD stage 5, in whom serum cortisol-to-cortisone (F/E) was measured as a biomarker of 11 beta HSD2 activity. A validation cohort (n = 101) enrolled only individuals with normal kidney function (eGFR >= 60 mL/min/1.73 m(2)) in whom 11 beta HSD2 activity was assessed via serum F/E and 11-hydroxy-to-11-keto androgen (11OH/K) ratios following multiple maneuvers: oral sodium suppression test, dexamethasone suppression test (DST), and ACTH-stimulation test (ACTHstim). Results In the discovery cohort, lower eGFR was associated with higher F/E (P-trend < .001). Similarly, in the validation cohort, with normal eGFR, an inverse association between eGFR and both F/E and 11OH/K ratios was observed (P-trend < .01), which persisted following DST (P-trend < .001) and ACTHstim (P-trend < .05). The fractional excretion of potassium, a marker of renal MR activity, was higher with higher F/E (P-trend < .01) and with lower eGFR (P-trend < .0001). Conclusion A continuum of declining 11 beta HSD2 activity was observed with progressively lower eGFR in individuals spanning a wide spectrum of kidney function, including those with apparently normal kidney function. These findings implicate cortisol-mediated MR activation in the pathophysiology of hypertension and cardiovascular disease in CKD.
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    PS 10-19 Serum cortisone and cortisol/cortisone ratio as tool to identify subjects with severe and partial 11beta-hydroxysteroid dehydrogenase type 2 deficiencies
    (LIPPINCOTT WILLIAMS & WILKINS, 2016) Carvajal Maldonado, Cristian Andrés; Tapia Castillo, Alejandra; Martínez Aguayo, Alejandro Gregorio; Valdivia, Carolina; Campino Johnson, María Del Carmen; Baudrand Biggs, Rene Felipe; Allende Sanzana, Fidel Alejandro; Pinochet Valenzuela, Constanza; Iturrieta González, Virginia Andrea; Lizama, Jaime; Solari Gajardo, Sandra; Fardella Bello, Carlos Enrique
    Objective: To report the phenotype of patients with AME by clinical and biochemical study, and expanding the study to their families and unrelated subjects to assess the value of F/E ratio as a biomarker partial deficiency of 11βHSD2.Design and Method: We evaluated 2 AME patients and their families. Family 1: A 17 years-old male with a homozygous Asp223Asn (D223N) mutation in HSD11B2, his mother (33 years) and sister (8 years); and Family 2: A 2 years-old girl with a homozygous Arg213Cys (R213C) mutation in HSD11B2, his father (30 years), her mother (30 years) and sister (6 years). We measured serum potassium, aldosterone, plasma renin activity (PRA), microalbuminuria, NGAL and F/E ratio (HPLC-MS). Reference ranges (RR), percentiles (p) and cut-off points for F, E and F/E serum were determined on data obtained from adult and pediatric normotensive subjects (F/E children RR: 1.63 to 5.15 and F/E adults RR:2.6–7.8]). Genetic analyses were performed by PCR-HRM and DNA sequencing.Results: Family 1: Index case (mut D223N) with classical AME features and a high serum F/E ratio (28.8 (> p99)). His mother and sister were normotensive and heterozygous for the same mutation D223N without clinical and biochemical abnormalities but with high F/E ratios (13.1 (p97) and 7.4 (p97)), respectively). Family 2: Index case (mut R213C) with classical AME and and a high F/E (175 (>p99)). His father, mother and sister were heterozygous for R123C, and are clinically and biochemically normal except for high F/E ratios (p92, p93 and p85, respectively).Conclusions: A F/E ratio greater than p90 –often associated to a cortisone lesser than p30- in relatives of subjects with AME suggests that partial heterozygous alterations or deficit in HSD11B2 are able to be identified by studying the serum cortisone and F/E ratio without prior clinical or biochemical features of classic AME such as AH, suppressed PRA and hypokalemia.
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    Serum cortisol and cortisone as potential biomarkers of partial 11β-hydroxysteroid dehydrogenase type 2 deficiency
    (2018) Carvajal Maldonado, Cristián Andrés; Tapia Castillo, Alejandra; Valdivia, Carolina P.; Allende, Fidel; Solari Gajardo, Sandra; Lagos Arévalo, Carlos Fernando; Campino Johnson, María del Carmen; Martínez Aguayo, Alejandro Gregorio; Vecchiola Cárdenas, Andrea Paola; Pinochet, Constanza
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    Sodium intake is associated with endothelial damage biomarkers and metabolic dysregulation
    (2018) Campino Johnson, María del Carmen; Baudrand Biggs, René; Valdivia, Carolina A.; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Tapia Castillo, Alejandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; García, Lorena; Allende, Fidel
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    The Expression of RAC1 and Mineralocorticoid Pathway-Dependent Genes are Associated With Different Responses to Salt Intake
    (2015) Tapia Castillo, Alejandra; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Hill, Caroline; Allende, Fidel; Vecchiola Cárdenas, Andrea Paola; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Baudrand Biggs, René; Kalergis Parra, Alexis Mikes; Fardella B., Carlos; Tapia Castillo, Alejandra; Carvajal Maldonado, Cristián Andrés; Campino Johnson, María del Carmen; Hill, Caroline; Allende, Fidel; Vecchiola Cárdenas, Andrea Paola; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Baudrand Biggs, René; Kalergis Parra, Alexis Mikes; Fardella B., Carlos
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    The role of sex hormones in aldosterone biosynthesis and their potential impact on its mineralocorticoid receptor
    (2024) Vecchiola Cárdenas, Andrea Paola; Uslar N., Thomas; Friedrich, Isidora; Aguirre, Joaquín; Sandoval, Alejandra; Carvajal, Cristian A.; Tapia Castillo, Alejandra; Martínez García, Alejandra Constanza; Fardella B., Carlos
    Blood pressure (BP) regulation is a complex process involving various hormones, including aldosterone and its mineralocorticoid receptor. Mineralocorticoid receptor is expressed in several tissues, including the kidney, and plays a crucial role in regulating BP by controlling the sodium and water balance. During different stages of life, hormonal changes can affect mineralocorticoid receptor activity and aldosterone levels, leading to changes in BP. Increasing evidence suggests that sex steroids modulate aldosterone levels. Estrogens, particularly estradiol, mediate aldosterone biosynthesis by activating classical estrogen receptors and the G protein-coupled receptor. Progesterone acts as an anti-mineralocorticoid by inhibiting the binding of aldosterone to the mineralocorticoid receptor. Moreover, progesterone inhibits aldosterone synthase enzymes. The effect of testosterone on aldosterone synthesis is still a subject of debate. However, certain studies show that testosterone downregulates the mRNA levels of aldosterone synthase, leading to decreased plasma aldosterone levels.